WBR0485
| Author | [[PageAuthor::Rim Halaby, M.D. [1], Alison Leibowitz [2] (Reviewed by Alison Leibowitz)]] |
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| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pathology, MainCategory::Pathophysiology |
| Sub Category | SubCategory::Hematology |
| Prompt | [[Prompt::An 18-month-old male is brought to an outpatient hematology department with pallor, beginning upon birth. The child has been admitted to the hospital multiple times for severe pallor and receives blood transfusions every couple of months, beginning when he was 2-months-old. He has been developing normally. The patient's family had recently migrated from Pakistan, and the mother denies any similar manifestations in the family. Upon physical exam, you note pallor, frontal bossing, and hepatomegaly, 4 cm below the costal margin. Blood work-up is significant for anemia (Hb= 6.7 g/dL) and the findings upon blood smear are illustrated below. Which of the following mutations is most likely associated with the patient's condition?
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| Answer A | AnswerA::HbA Alpha-chain mutation |
| Answer A Explanation | [[AnswerAExp::Alpha chain mutations, which do not cause ringed sideroblasts upon blood smear, are frequently observed in in alpha-thalassemia.]] |
| Answer B | AnswerB::HbA Beta-chain mutation |
| Answer B Explanation | [[AnswerBExp::Beta chain mutations, which do not cause ringed sideroblasts upon blood smear, are frequently observed in beta-thalassemia.]] |
| Answer C | AnswerC::Delta-ALA synthase mutation |
| Answer C Explanation | AnswerCExp::See explanation. |
| Answer D | AnswerD::Spectrin and Ankyrin mutations |
| Answer D Explanation | AnswerDExp::Spectrin and Ankyrin mutations, which do not cause ringed sideroblasts upon blood smear, are frequently observed in hereditary sperocytosis. |
| Answer E | AnswerE::Glucose-6-Phosphate Dehydrogenase mutaion |
| Answer E Explanation | AnswerEExp::Glucose-6-Phosphate Dehydrogenase mutations, which do not cause ringed sideroblasts upon blood smear, are frequently observed in G6PD deficiency. |
| Right Answer | RightAnswer::C |
| Explanation | [[Explanation::Congenital sideroblastic anemia, an inherited disease, is characterized by hypochromic microcytic anemia, iron overload, and ringed sideroblasts upon blood smear and bone marrow biopsy. The most frequently occurring pattern of inheritance is X-linked, secondary to a mutation in the ALAS2 gene, producing a defective ALA synthase enzyme. Since ALA synthase catalyses the first step in heme synthesis, deficiency leads to mitochondrial iron accumulation manifesting as ringed sideroblasts. Congenital sideroblastic anemia frequently is treated with oral vitamin B6, as pyridoxine is a key cofactor in the ALAS reaction. The age at presentation, severity of the anemia, and response to vitamin B6 vary. Diagnosis of Congenital sideroblastic anemia is dependent of on the findings of bone marrow biopsy or smear, HPLC, and blood iron work-up. Prussian blue staining is often used to detect the iron rings. Prussian blue involves a non-enzymatic reaction of ferrous iron with ferrocyanide, forming ferric-ferrocyanide, which is blue in color. Educational Objective: Congenital sideroblastic anemia, an inherited disease caused by a mutation in the ALAS2 gene, produces a defective ALA synthase enzyme. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Sideroblastic anemia, WBRKeyword::Sideroblasts, WBRKeyword::ALA synthase mutation, WBRKeyword::genetics, WBRKeyword::blood smear, WBRKeyword::inheritance, WBRKeyword::pattern of inheritance, WBRKeyword::mutations, WBRKeyword::X-linked |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |
